Abuse of prescription opioids such as oxycodone has risen dramatically throughout the last decade and is considered a public health problem of epidemic proportion. Treatment options for prescription opioid addiction are similar to those for heroin, and most frequently incorporate maintenance pharmacotherapy with methadone, buprenorphine, or naltrexone. There is, however, insufficient information to evaluate the clinical utility of either agonist-based or antagonist-based pharmacotherapies for prescription opioid addiction. Moreover, although relapse to prescription opioids is well-documented in human abusers, there is almost no information comparing the effectiveness of agonist or antagonist maintenance regimens in reducing relapse to drug seeking in either humans or laboratory animals. To address this gap in knowledge, we will study how chronic exposure to maintenance pharmacotherapies modifies the relapse-related priming effects of prescription opioids and drug-paired environmental stimuli in nonhuman primates. Our research plan is based on solid preliminary data and previous findings suggesting that the ability of prescription opioids to induce relapse-related behavior during maintenance therapy depends critically on the maintenance drug and the agonist efficacy of the prescription opioid. In our proposed studies, we will use a novel drug/food choice procedure to determine the ability of selected prescription opioids to induce drug-seeking behavior in monkeys with prior histories of persistent oxycodone self-administration before, during and after chronic maintenance regimens with methadone, buprenorphine or naltrexone. These investigations will provide needed preclinical data with direct relevance for understanding pharmacological and behavioral factors that influence relapse vulnerability under different therapeutic maintenance conditions. Our studies also will incorporate a novel performance- based assay to determine threshold values for thermal nociception. We will use this assay to address the complex and clinically difficult issue of changes in the anti-nociceptive effects of prescription opioids before, during and after different maintenance regimens. The impact of our proposed research lies in its ability to provide preclinical information that ultimately can improve the management of prescription opioid addiction and relapse as well as provide guidance regarding the clinical use of prescription opioids for pain management during and after opioid agonist and antagonist maintenance regimens.